Hormones use and breast cancer risk

By Dr. Ananya Mandal, MDApr 1 2012

According to latest research long-term use of any type of hormones to ease menopause symptoms can raise a woman's risk of breast cancer.

Scientists know that taking pills that combine estrogen and progestins - the most common type of hormone therapy - can increase breast cancer risk. But women who no longer have a uterus can take estrogen alone, which was thought to be safe and possibly even slightly beneficial in terms of cancer risk.

However this new study shows if the pills are used for many years the results are not beneficial. The study tracked the health of about 60,000 nurses and found that use of any kind of hormones for 10 years or more slightly raised the chances of developing breast cancer. “There's a continued increase in risk with longer durations of use and there does not appear to be a plateau,” said study leader Wendy Chen of Brigham and Women's Hospital in Boston.

“It's hard to be surprised that if you keep taking it, sooner or later it's going to raise risk,” said Robert Clarke of Georgetown University's Lombardi Comprehensive Cancer Center. The study was discussed at the 2012 American Association for Cancer Research Annual Meeting in Chicago at a press conference on April 1.

In another study researchers have found that in mouse models at least, there is a strong connection between autoimmune arthritis and increased aggressiveness in metastatic breast cancer.

The connection appears to involve the tendency of autoimmune arthritis to increase production of mast cells, an immune cell type that increases inflammation and that is prevalent in metastatic tumors. By blocking a key receptor, the researchers were able to affect the interaction between the cancer and mast cells and lessen metastasis.

The new-found interaction between the two diseases may also suggest a possible treatment. A potential relationship between metastatic breast cancer and autoimmune arthritis, as suggested by past epidemiological studies, has led researchers from the University of North Carolina at Charlotte to perform a series of mouse model experiments that appear to confirm the connection.

“Epidemiological studies have implied that breast cancer survival is significantly lower in patients who also had autoimmune arthritis,” noted Pinku Mukherjee, Irwin Belk Distinguished Scholar of Cancer Research at UNC Charlotte, whose lab conducted the experiments. “As there is no obvious reason this should be so, we were interested in exploring possible cancer mechanisms that might explain why.”

In previously published studies, UNC Charlotte cancer researcher Lopamudra Das Roy and her mentor Mukherjee established that breast cancer associated metastases were significantly higher in arthritic mice, with a threefold increase in lung metastases and a twofold increase in bone metastases.

In their most recent work, the researchers found that mast cells and their associated inflammation are present in larger numbers in the bones and lungs of arthritic mice than they are in non-arthritic mice. Their findings point to a relationship between the cKit receptor found on mast cells and the transmembrane stem cell factor (SCF) ligand found on metastatic breast cancer cells. The interaction between SCF and cKit appears to play a critical role in facilitating metastasis. “We confirmed the relationship we suspected between autoimmune disease and metastastic breast cancer cells,” Mukherjee said. “This is an exciting result for us because it confirms an interesting interdependence between cancer metastasis and a specific component of the immune system.” In future studies, the researchers plan to examine the presence of mast cells in human tumor samples.

The study results will be presented by Lopamudra Das Roy, Research Assistant Professor at UNC Charlotte, and Mukherjee at the 2012 American Association for Cancer Research Annual Meeting in Chicago at a press conference on April 1.